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Clozapine plasma levels and dosing strategies in patients with treatment-refractory schizophrenia

Published online by Cambridge University Press:  13 June 2014

Peter F Buckley ,
Philip Cola ,
Mitsuru Hasegawa ,
Christine Lys  and
Paul Thompson
Peter F Buckley
Affiliation:
Department of Psychiatry, Case Western Reserve University, University Hospitals of Cleveland, Hanna Pavilion, 2040 Abington Road, Cleveland, Ohio 44106, USA
Philip Cola
Affiliation:
Department of Psychiatry, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106, USA
Mitsuru Hasegawa
Affiliation:
Department of Psychiatry, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106, USA
Christine Lys
Affiliation:
Department of Psychiatry, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106, USA
Paul Thompson
Affiliation:
Department of Psychiatry, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106, USA
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Abstract

Objective: To determine the effect on clinical response to clozapine of increasing the plasma levels of clozapine and its major metabolite N-desmethylclozapine in 19 patients with schizophrenia who had plasma clozapine levels ≤ 370ng/ml, a level previously determined to identify patients who were unlikely to have an adequate response to clozapine.

Method: The dosage of clozapine was increased by 20% in 11 patients and left unaltered in the other eight patients. Clozapine and N-desmethylclozapine plasma levels were measured after six weeks at the higher dose.

Results: Nine of the 11 patients in whom clozapine dosage was increased subsequently achieved plasma clozapine levels ≥ 370ng/ml. However, in this group of patients who already had partially responded to clozapine, increasing the dosage of clozapine did not produce additional clinical improvement.

Conclusion: Clozapine plasma levels are useful in clinical practice to guide dosage strategies. However, these results suggest that increasing the dosage of clozapine to achieve plasma levels ≥ 370ng/ml is unlikely to produce further improvement in patients who have already achieved a partial response to clozapine at plasma levels ≤ 370ng/ml.

Type
Original Papers
Information
Irish Journal of Psychological Medicine , Volume 14 , Issue 3 , September 1997 , pp. 85 - 88
Copyright
Copyright © Cambridge University Press 1997

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References

1.Kane, JM, Honigfeld, G, Singer, Jet al.Clozapine for the treatment-resistant schizophrenic. Arch Gen Psychiatry 1988; 45: 789–96.CrossRefGoogle ScholarPubMed
2.Meltzer, HY. Treatment of the neuroleptic-non-responsive schizophrenic patient. Schiz Bull 1992; 18: 515–42.CrossRefGoogle ScholarPubMed
3.Meltzer, HY. Dimensions of outcome with clozapine. Br J Psychiatry 1992; 160(17): 36–43.CrossRefGoogle Scholar
4.Hagger, C, Buckley, P, Kenny, JT, et al.Improvement in cognitive functions and psychiatric symptoms in treatment-refractory schizophrenic patients receiving clozapine. Biol Psychiatry 1993; 34: 702–12.CrossRefGoogle ScholarPubMed
5.Lee, MA, Thompson, PA, Meltzer, HY. Effects of clozapine on cognitive function in schizophrenia. J Clin Psychiatry 1994; 55(9, suppl B): 82–7.Google ScholarPubMed
6.Goldberg, TE, Weinberger, DR. Neuropsychological function and clozapine treatment. J Clin Psychiatry 1994; 55(Suppl 9): 88–92.Google Scholar
7.Meltzer, HY, Burnett, S, Bastani, B, et al.Effect of six months of clozapine treatment on the quality of life of chronic schizophrenic patients. Hosp Comm Psychiatry 1990; 41(8): 892–7.Google ScholarPubMed
8.Meltzer, HY. Duration of a clozapine trial in neuroleptic-resistant schizophrenia. Arch Gen Psychiatry 1989; 46: 672.CrossRefGoogle ScholarPubMed
9.Povlsen, J, Noring, U, Fog, Ret al.Tolerability and therapeutic effect of clozapine: a retrospective investigation of 216 patients, treated with clozapine for up to 12 years. Acta Psychiatr Scand 1985; 71:176–85.CrossRefGoogle Scholar
10.Hiemke, C, Weigmann, H, Hartter, S. Elevated levels of clozapine in serum after addition of fluvoxamine. J Clin Psychopharmacol 1994; 14(4): 279–81.CrossRefGoogle ScholarPubMed
11.Perry, PJ, Miller, DD, Arndt, SVet al.Clozapine and non-clozapine plasma concentrations and clinical response of treatment-refractory schizophrenic patients. Am J Psychiatry 1991; 148: 231–5.Google Scholar
12.Hasegawa, M, Gutierrez-Esterinou, R, Way, Let al.Relationship between clinical efficacy and clozapine concentrations in plasma in schizophrenia. Effect of Smoking. J Clin Psychopharmacol 1993; 13(6): 383–90.CrossRefGoogle ScholarPubMed
13.Lieberman, JA, Kane, JM, Safferman, AZ. Predictors of response to clozapine. J Clin Psychiatry 1994; 55(9, suppl B): 126–8.Google ScholarPubMed
14.Miller, DD, Fleming, F, Holman, TLet al.Plasma clozapine concentrations as a predictor of clozapine response: a follow-up study. J Clin Psychiatry 1994; 55(9, suppl B): 117–21.Google ScholarPubMed
15.Potkin, SG, Bera, R, Gulasekaram, Bet al.Plasma clozapine concentrations predict clinical response in treatment-resistant schizophrenia. J Clin Psychiatry 1994; 55(9, suppl B): 133–6.Google ScholarPubMed
16.Ackenheil, M, Brau, H, Burkhart, Aet al.Antipsychotische wirksamkeit im verhaltnis sum plasmaspiegel von Clozapin. Arzneimittelforschung 1976; 26: 1156–8.Google Scholar
17.Thorup, M, Fog, R. Clozapine treatment of schizophrenic patients: plasma concentration and coagulation factors. Acta Psychiatr Scand 1977; 55:123–6.CrossRefGoogle ScholarPubMed
18.Brau, VH, Burkhart, A, Pacha, Wet al.Benziehungen zwischen Wirkungen und Plasmaspiegel von Clozapine. Arzneimittelforschung 1978: 1300–1.Google Scholar
19.American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 3rd ed. Revised. Washington DC, 1987.Google Scholar
20.Endicott, J, Spitzer, RL. A diagnostic interview. The Schedule for Affective Disorders and Schizophrenia. Arch Gen Psychiatry 1978; 35: 837–44.CrossRefGoogle ScholarPubMed
21.Rhodes, HM, Overall, JE. The semistructured BPRS interview and rating guide. Psychopharmacol Bull 1988; 10: 101–4.Google Scholar
22.Lovdahl, JM, Perry, PJ, Miller, DD. The assay of clozapine and N-desmethylclozapine in human plasma by high performance liquid chromatography. Ther Drug Monit 1991; 13: 69–72.CrossRefGoogle ScholarPubMed
23. SAS. SAS Institute Inc, 1995.Google Scholar
24.Kronig, MH, Munne, RA, Szymanski, Set al.Plasma clozapine levels and clinical response in treatment-refractory schizophrenia. Am J Psychiatry 1995; 152: 179–82.Google Scholar